Sacituzumab Govitecan Induces Durable Responses in NSCLC

Author(s):

Results from a single-arm, multicenter trial showed that the antibody-drug conjugate sacituzumab govitecan (IMMU-132) was well-tolerated and produced a median duration of response of 6.0 months in previously treated patients with metastatic non–small cell lung cancer.

Rebecca S. Heist, MD

The results, which were published online in the Journal of Clinical Oncology, showed a median progression-free survival of 5.2 months (95% CI, 3.2-7.1) and median overall survival of 9.5 months (95% CI, 5.9-16.7) in the intent-to-treat population. The clinical benefit rate of 43%.

“This study shows that IMMU-132 can be effective in patients who did not respond to or progressed after multiple treatments, including immune checkpoint inhibitors, although these results are early and in a small number of patients,” first author Rebecca S. Heist, MD, assistant professor in Medicine, Massachusetts General Hospital, Harvard Medical School, and colleagues wrote. “We also observed activity in squamous cells, a subtype with a high unmet need.”

Sacituzumab govitecan is a novel antibody-drug conjugate that targets Trop-2, a 46-kD glycoprotein overexpressed in many epithelial cancers. High Trop-2 expression correlates with poor prognosis in many cancers, including NSCLC.

Results from a previous phase I trial, published by Starodub et al in 2015,² showed encouraging therapeutic activity in advanced solid cancers. These results come from a single-arm expansion of the previous trial, evaluating the activity of sacituzumab govitecan in patients with metastatic NSCLC who progressed after at least 1 prior therapy.

Fifty-four patients enrolled in the study from December 2013 to March 2016. Eight patients received a starting dose of 8 mg/kg of sacituzumab govitecan and 46 started at 10 mg/kg. Most patients (83%) had nonsquamous disease.

Thirty-one patients died by the October 14, 2016, data cutoff, 3 were lost to follow-up, and 20 were still alive. Median follow-up was 9.0 months (range, 4.4-25.3), including 6 patients who remained on study.

Investigators administered more than 800 doses of sacituzumab govitecan for a median of 5 cycles per patient and a median treatment duration of 3.3 months.

Patients in the study had undergone a median of 3 prior lines of therapy for metastatic disease (range, 2-7), and all patients had received prior platinum-based therapy. Forty patients (74%) had at least 1 prior platinum-based chemotherapy with a taxane; the remaining 14 patients also received gemcitabine and/or pemetrexed (Alimta).

Eighteen patients (33%) had received a prior checkpoint inhibitor and 17 (32%) had received an EGFR inhibitor.

Forty-seven patients were available for response assessment. Of those, 67% had a reduction of tumor size from baseline and 19% had confirmed partial response. The objective response rate in the intention-to-treat was 17% (9 of 54 patients).

Median time to tumor response was 3.8 months (1.8-11.6) and the median duration of response was 6.0 months (95% CI, 4.8-8.3) for those 9 patients, with 2 of these responses still ongoing (one at ≥7.6 months, the other at ≥19.1 months).

Four other patients have continued therapy, including 1 responder who stayed on-study after physicians discovered and treated a brain lesion with radiation.

Among the 7 response-assessable patients who had squamous cell histology, 43% had >30% reductions of their target lesions, including 1 partial response and 2 with stable disease, 1 for nearly 6 months.

Fourteen of the 18 patients who had a prior immunotherapy with a checkpoint inhibitor were assessable for response. Two had partial response, 7 had stable disease, and 5 had durable disease control that lasted >4 months. Investigators said that these results suggest that even patients who developed refractory or relapsed disease while receiving immunotherapy could benefit from sacituzumab govitecan.

Neutropenia (28%) was the most common grade 3 or higher adverse event (AE), and was the primary cause for dose reductions, which occurred in 23 (43%) patients. Researchers said that after the initial reduction, additional dose reductions were rare.

Other serious AEs that occurred in ≥5% of patients were leukopenia (9%), pneumonia (9%), diarrhea (7%), nausea (7%), and fatigue (6%). Only 2 patients (4%) experienced febrile neutropenia.

One patient with grade 3 pneumonia after 8 cycles and another with grade 3 recurrent pruritus after 2 cycles discontinued the study.

The investigators wrote that immunohistochemistry staining of tumor specimens did not produce enough evidence to determine whether Trop-2 staining is a useful biomarker for predicting response.

References

Heis RS, Guarino MJ, Masters G, et al. Therapy of advanced non—small-cell lung cancer with an SN-38-anti-trop-2 drug conjugate, sacituzumab govitecan [published online May 26, 2017]. J Clin Oncol. doi: 10.1200/JCO.2016.72.1894.
Starodub AN, Ocean AJ, Shah MA, et al. First-in-human trial of a novel anti-Trop-2 antibody-SN-38 conjugate, sacituzumab govitecan, for the treatment of diverse metastatic solid tumors. Clin Cancer Res. 2015;21(17):3870-3878. doi: 10.1158/1078-0432.CCR-14-3321.